P1195: A PROSPECTIVE STUDY OF TARGETED SEQUENTIAL IMMUNOTHERAPY. IN PATIENTS WITH RELAPSED REFRACTORY PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA.
Authors: Yuelu Guo, Kai Hu, Xiaoyan Ke, Teng Xu, Shaomei Feng, Peihao Zheng, Lixia MA, Fan Yang, Hui Shi, Biping Deng, Liu Rui, Zhonghua Fu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: PMBCL is most common in young women, with a 5-year survival rate of up to 65% ，but limited therapeutic options in relapsed refractory primary mediastinal large B-cell lymphoma (rrPMBCL). CART treatment appears to be effective in rrPMBCL, but data is limited. There is a scarcity of large-scale data on the molecular characteristics of PMBCL patients and their relationship to targeted immunotherapy. This study also investigated the relationship between rrPMBCL molecular characteristics and targeted immunotherapy in order to provide a foundation for the precise selection of targeted immunotherapy Aims: To better understand the potential of targeted sequential immunotherapy (PD1 monoclonal antibody combined with chemotherapy as a tumor-reducing regimen bridging to CART therapy) in rrPMBCL. To investigate the factors that influence this treatment modality and its relationship with gene mutations in order to provide a foundation for selecting a treatment regimen for rrPMBCL. Methods: The impact of targeted sequential immunotherapy regimens on survival and prognosis was quantified, and clinical and molecular characteristics of rrPMBCL patients were examined and correlated with treatment regimens and survival before and after treatment. Results: There were 22 patients with rrPMBCL who met the inclusion criteria and 19 patients who completed targeted sequential immunotherapy, with an ORR of 53% (10/19) and a CR rate of 53%. All 22 patients received tumor-reducing chemotherapy in combination with PD1 monoclonal antibody, with a 3-month ORR of 8/22 (36.4%) and CR of 7/22 (31.8%) for tumor-reducing chemotherapy. After bridging to CART, the final CR rate was 7/8 (97%) in patients who achieved PR or higher with the PD1 monoclonal antibody tumor-reducing regimen and 3/11 (27%) in patients who did not achieve remission with the tumor-reducing regimen. The 3-month ORR of a PD1 monoclonal antibody tumor-reducing chemotherapy regimen was significantly higher in the STAT6-positive mutation group compared to the non-mutation group (OR=23,P=0.0402). The B2M-positive mutation group had a significantly higher 3-month CR rate than the non-mutation group (OR=12, P=0.0317). The best of response(BOR) in targeted sequential immunotherapy was higher in the PD1 monoclonal anti-tumor reduction chemotherapy PR group (OR=18.67,P=0.0149), the PD1 monoclonal anti-tumor reduction chemotherapy up to CR group (OR=12.00,P=0.0399), and the presence of B2M mutation group (OR=14,P=0.0185). PFS was significantly longer in patients with an IPI score of 0-2 (HR=0.22, P=0.0358), PD1 monoclonal anti-tumor reduction chemotherapy at PR and above (HR=0.12, P=0.0493), and a B2M mutation (HR=0.16, P=0.0243). IPI score 0-2 (HR=0.14, P=0.022), SOCS1 mutation (HR=0.09, P=0.0083), and B2M mutation (HR=0.21, P=0.0553) all resulted in significantly longer OS. Summary/Conclusion: Treatment for rrPMBCL can include targeted sequential immunotherapy. If a PD1 tumor reduction regimen achieves PR or higher, patients should begin CART as soon as possible. B2M mutation-positive, SOCS1-positive patients can benefit from targeted sequential immunotherapy. Keywords: Diffuse large cell lymphoma, CAR-T, Immune therapy